Trimodulin Supports Antibacterial Defence and Restricts Inflammation in Preclinical Pneumonia Models.

IF 21 1区 医学 Q1 RESPIRATORY SYSTEM
Geraldine Nouailles,Romina Bischoff,Kerstin Linke,Alexander Taylor,Birgitt Gutbier,Peter Pennitz,Cengiz Goekeri,Sandra Kunder,Anne Voß,Theresa C Brömel,Olivia Kershaw,Miha Milek,Vadim Farztdinov,Michael Mülleder,Sabrina Weissmüller,Corina C Heinz,Mayken Visser,Fabian Bohlaender,Katharina Ahrens,Dieter Beule,Achim D Gruber,Martin Koenig,Martin Witzenrath
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Abstract

BACKGROUND Severe pneumonia (sCAP) remains a global health challenge with high mortality despite advances in antibiotic therapy and supportive care. Immunoglobulin (Ig) therapies, especially IgM-containing ones, have shown promise in enhancing host defence and reducing inflammation. The CIGMA trial highlighted trimodulin's potential to lower mortality of sCAP patients with high C-reactive protein and low IgM levels. METHODS We investigated the protective effects of trimodulin on clinical status, bacterial burden, lung integrity, and inflammatory responses in murine models of lung injury, including both ventilator-induced lung injury (VILI) and infection-induced models with non-sterile inflammation. FINDINGS In mice, trimodulin significantly protected against lethal pneumococcal pneumonia by reducing bacterial burden and disease severity while preserving alveolar barrier integrity and limiting lung edema. The antibacterial action of trimodulin was mediated through opsonophagocytosis, and its anti-inflammatory effects operated independently of the latter. When combined with ampicillin, trimodulin exhibited enhanced suppression of inflammation. INTERPRETATION Our findings in preclinical pneumonia models suggest that trimodulin could be a promising therapy for sCAP patients. We provide evidence that trimodulin enhances host defence, reduces detrimental pulmonary inflammation and barrier dysfunction, and limits pulmonary edema, which may explain its beneficial effects observed in sCAP patients.
三联调素在临床前肺炎模型中支持抗菌防御并限制炎症。
背景:尽管抗生素治疗和支持性护理取得了进展,但严重肺炎(sCAP)仍然是一个全球卫生挑战,死亡率很高。免疫球蛋白(Ig)疗法,特别是含有igm的疗法,在增强宿主防御和减少炎症方面显示出希望。CIGMA试验强调了trimodulin在降低高c反应蛋白和低IgM水平sCAP患者死亡率方面的潜力。方法研究三调素对小鼠肺损伤模型的临床状态、细菌负荷、肺完整性和炎症反应的保护作用,包括呼吸机诱导肺损伤(VILI)和感染诱导非无菌炎症模型。在小鼠中,三调素通过降低细菌负担和疾病严重程度,同时保持肺泡屏障完整性和限制肺水肿,显著保护小鼠免受致命性肺炎球菌肺炎。三调素的抑菌作用是通过调理噬细胞作用介导的,其抗炎作用独立于调理噬细胞作用。当与氨苄西林联合使用时,三调素表现出增强的炎症抑制作用。我们在临床前肺炎模型中的研究结果表明,三调素可能是sCAP患者的一种有希望的治疗方法。我们提供的证据表明,三调素增强宿主防御,减少有害的肺部炎症和屏障功能障碍,并限制肺水肿,这可能解释了其在sCAP患者中观察到的有益作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
European Respiratory Journal
European Respiratory Journal 医学-呼吸系统
CiteScore
27.50
自引率
3.30%
发文量
345
审稿时长
2-4 weeks
期刊介绍: The European Respiratory Journal (ERJ) is the flagship journal of the European Respiratory Society. It has a current impact factor of 24.9. The journal covers various aspects of adult and paediatric respiratory medicine, including cell biology, epidemiology, immunology, oncology, pathophysiology, imaging, occupational medicine, intensive care, sleep medicine, and thoracic surgery. In addition to original research material, the ERJ publishes editorial commentaries, reviews, short research letters, and correspondence to the editor. The articles are published continuously and collected into 12 monthly issues in two volumes per year.
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